Amelioration of Impaired Cerebral Metabolism After Severe Acidotic Ischemia by Tirilazad Posttreatment in Dogs

Background and Purpose Acidosis may contribute to ischemic injury by mobilizing iron because the iron chelator deferoxamine improves early metabolic recovery from hyperglycemic ischemia. Mobilized iron may then promote oxygen radical-induced lipid peroxidative injury during reperfusion. We tested the hypothesis that administration of the antioxidant tirilazad at the start of reperfusion improves early metabolic recovery after severe acidotic ischemia and ameliorates depletion of the endogenous antioxidant glutathione. Methods In anesthetized dogs, arterial glucose concentration was increased to 500 to 600 mg/dL and global incomplete cerebral ischemia was produced for 30 minutes by ventricular fluid infusion to reduce perfusion pressure to 10 to 12 mm Hg. Metabolic recovery and intracellular pH were measured by phosphorus MR spectroscopy. In the first experiment, four groups of eight dogs each received either vehicle or 0.25, 1, or 2.5 mg/kg of tirilazad mesylate at reperfusion. Cerebral blood flow was mea...